One of the popular approaches in controlling drug delivery from the polymeric carriers is suitably achieved by the inclusion of crosslinking agents into the formulations at different concentrations. Nevertheless, addition of the chemical crosslinkers such as glutaraldehyde, formaldehyde etc, used in the drug delivery systems causes very serious cytotoxic reactions. These chemical crosslinking agents did not offer any significant advantageous effects when compared to the natural crosslinking agents for instance genipin, which is quite less toxic, biocompatible and offers very stable crosslinked products. Based on the earlier reports the safety of this particular natural crosslinker is very well established, since it has been widely used as a Chinese traditional medicine for long-time, isolated from fruits of the plant Gardenia jasminoides Ellis. This concise article largely portrayed the value of this unique natural crosslinker, utilized in controlling the drug delivery from the various formulations.
Matched MeSH terms: Drug Delivery Systems/methods*
The involvement of recent technologies, such as nanotechnology and three-dimensional printing (3DP), in drug delivery has become the utmost importance for effective and safe delivery of potent therapeutics, and thus, recent advancement for oral drug delivery through 3DP technology has been expanded. The use of computer-aided design (CAD) in 3DP technology allows the manufacturing of drug formulation with the desired release rate and pattern. Currently, the most applicable 3DP technologies in the oral drug delivery system are inkjet printing method, fused deposition method, nozzle-based extrusion system, and stereolithographic 3DP. In 2015, the first 3D-printed tablet was approved by the US Food and Drug Administration (FDA), and since then, it has opened up more opportunities in the discovery of formulation for the development of an oral drug delivery system. 3DP allows the production of an oral drug delivery device that enables tailor-made formulation with customizable size, shape, and release rate. Despite the advantages offered by 3DP technology in the drug delivery system, there are challenges in terms of drug stability, safety as well as applicability in the clinical sector. Nonetheless, 3DP has immense potential in the development of drug delivery devices for future personalized medicine. This article will give the recent advancement along with the challenges of 3DP techniques for the development of oral drug delivery. Graphical abstract.
One of the novel and progressive technology employed in pharmaceutical manufacturing, design of medical device and tissue engineering is three-dimensional (3D) printing. 3D printing technologies provide great advantages in 3D scaffolds fabrication over traditional methods in the control of pore size, porosity, and interconnectivity. Various techniques of 3D-printing include powder bed fusion, fused deposition modeling, binder deposition, inkjet printing, photopolymerization and many others which are still evolving. 3D-printing technique been employed in developing immediate release products, various systems to deliver multiple release modalities etc. 3D printing has opened the door for new generation of customized drug delivery with built-in flexibility for safer and effective therapy. Our mini-review provides a quick snapshot on an overview of 3D printing, various techniques employed, applications and its advancements in pharmaceutical sciences.
The novel Coronavirus disease (COVID-19) is an epidemic disease that appeared at the end of the year 2019 with a sudden increase in number and came to be considered as a pandemic disease caused by a viral infection which has threatened most countries for an emergency search for new anti-SARS-COV drugs /vaccines. At present, the number of clinical trials is ongoing worldwide on different drugs i.e. Hydroxychloroquine, Remedisvir, Favipiravir that utilize various mechanisms of action. A few countries are currently processing clinical trials, which may result in a positive outcome. Favipiravir (FPV) represents one of the feasible treatment options for COVID-19, if the result of the trials turns out positive. Favipiravir will be one of the developed possibly authoritative drugs to warrant benefits to mankind with large-scale production to meet the demands of the current pandemic Covid-19 outbreak and future epidemic outbreaks. In this review, the authors tried to explore key molecules, which will be supportive for devising COVID-19 research.
An orally-administered system for targeted, on-demand drug delivery to the gastrointestinal (GI) tract is highly desirable due to the high instances of diseases of that organ system and harsh mechanical and physical conditions any such system has to endure. To that end, we present an iron oxide nanoparticle/wax composite capsule coating using magnetic hyperthermia as a release trigger. The coating is synthesised using a simple dip-coating process from pharmaceutically approved materials using a gelatin drug capsule as a template. We show that the coating is impervious to chemical conditions within the GI tract and is completely melted within two minutes when exposed to an RF magnetic field under biologically-relevant conditions. The overall simplicity of action, durability and non-toxic and inexpensive nature of our system demonstrated herein are key for successful drug delivery systems.
pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.
This study aimed to develop a dual action, namely anti-inflammatory and antimicrobial, nanogels (NG) for the treatment of periodontitis using triclosan (TCS) and flurbiprofen (FLB). Triclosan, an antimicrobial drug, was prepared as nanoparticles (NPs) using poly-ε-caprolactone (PCL), while flurbiprofen, an anti-inflammatory drug, was directly loaded in a chitosan (CS) based hydrogel. The entwinement of both NPs and hydrogel loaded systems resulted in the NG. The characterisation data confirmed that the developed formulation consists of nanosized spherical structures and displays pH-dependent swelling/erosion and temperature-responsiveness. Besides, the NG exhibited adequate bioadhesiveness using the chicken pouch model and displayed antibacterial activity through the agar plate method. An in-vivo study of the NG on experimental periodontitis (EP) rats confirmed the dual antibacterial and anti-inflammatory effects which revealed an excellent therapeutic outcome. In conclusion, a dual action NG was successfully developed and proved to have superior therapeutic effects in comparison to physical mixtures of the individual drugs.
In endoscopic neurosurgery problems with haemostasis due to poor access exist. We have developed a system which allows the delivery of a variety of haemostatic agents in a more efficacious manner. The system has been used successfully in endoscopic skull base surgery and endoscopic surgery within the parenchyma of the brain using tube systems.
Matched MeSH terms: Drug Delivery Systems/instrumentation*; Drug Delivery Systems/methods
The aim of this paper was to introduce a new mechanism of thermal sensitivity in nanocarriers that results in a relatively low drug release at physiological temperature and rapid release of the encapsulated drug at hyperthermia and thermal ablation temperature range (40-60 °C).
Matched MeSH terms: Drug Delivery Systems/methods*
The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO₃/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO₃/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO₃/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO₃ nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.
The field of pharmaceutical technology is expanding rapidly because of the increasing number of drug delivery options. Successful drug delivery is influenced by multiple factors, one of which is the appropriate identification of materials for research and engineering of new drug delivery systems. Bacterial cellulose (BC) is one such biopolymer that fulfils the criteria for consideration as a drug delivery material.
Matched MeSH terms: Drug Delivery Systems/methods*
This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed "green nanomedicine". Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow.
Matched MeSH terms: Drug Delivery Systems/methods*
Natural polysaccharides are renewable with a high degree of biocompatibility, biodegradability, and ability to mimic the natural extracellular matrix (ECM) microenvironment. Comprehensive investigations of polysaccharides are essential for our fundamental understanding of exploiting its potential as bio-composite, nano-conjugate and in pharmaceutical sectors. Polysaccharides are considered to be superior to other polymers, for its ease in tailoring, bio-compatibility, bio-activity, homogeneity and bio-adhesive properties. The main focus of this review is to spotlight the new advancements and challenges concerned with surface modification, binding domains, biological interaction with the conjugate including stability, polydispersity, and biodegradability. In this review, we have limited our survey to three essential polysaccharides including cellulose, starch, and glycogen that are sourced from plants, microbes, and animals respectively are reviewed. We also present the polysaccharides which have been extensively modified with the various types of conjugates for combating last-ditch pharmaceutical challenges.
To realize the maximum therapeutic activity of medicine and protect the body from the adverse effects of active ingredients, drug delivery systems (DDS) featured with targeted transportation sites and controllable release have captured extensive attention over the past decades. Hydrogels with unique three-dimensional (3D) porous structures present tunable capacity, controllable degradation, various stimuli sensitivity, therapeutic agents encapsulation, and loaded drugs protection properties, which endow hydrogels with bred-in-the-bone advantages as vehicles for drug delivery. In recent years, with the impressive consciousness of the "back-to-nature" concept, biomass materials are becoming the 'rising star' as the hydrogels building blocks for controlled drug release carriers due to their biodegradability, biocompatibility, and non-toxicity properties. In particular, cellulose and its derivatives are promising candidates for fabricating hydrogels as their rich sources and high availability, and various smart cellulose-based hydrogels as targeted carriers under exogenous such as light, electric field, and magnetic field or endogenous such as pH, temperature, ionic strength, and redox gradients. In this review, we summarized the main synthetic strategies of smart cellulose-based hydrogels including physical and chemical cross-linking, and illustrated the detailed intelligent-responsive mechanism of hydrogels in DDS under external stimulus. Additionally, the ongoing development and challenges of cellulose-based hydrogels in the biomedical field are also presented.
Conventional cancer treatment techniques show several limitations including low or no specificity and consequently a low efficacy in discriminating between cancer cells and healthy cells. Recent nanotechnology developments have introduced smart and novel therapeutic nanomaterials that take advantage of various targeting approaches. The use of nanotechnology in medicine and, more specifically, drug delivery is set to spread even more rapidly than it has over the past two decades. Currently, many nanoparticles (NPs) are under investigation for drug delivery including those for cancer therapy. Targeted nanomaterials bind selectively to cancer cells and greatly affect them with only a minor effect on healthy cells. Gold nanoparticles (Au-NPs), specifically, have been identified as significant candidates for new cancer therapeutic modalities because of their biocompatibility, easy functionalization and fabrication, optical tunable characteristics, and chemophysical stability. In the last decade, there has been significant research on Au-NPs and their biomedical applications. Functionalized Au-NPs represent highly attractive and promising candidates for drug delivery, owing to their unique dimensions, tunable surface functionalities, and controllable drug release. Further, iron oxide NPs due to their "superparamagnetic" properties have been studied and have demonstrated successful employment in numerous applications. In targeted drug delivery systems, drug-loaded iron oxide NPs can accumulate at the tumor site with the aid of an external magnetic field. This can lead to incremental effectiveness in drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order for the application of iron oxide NPs in the human body to be realized, they should be biodegradable and biocompatible to minimize toxicity. This review illustrates recent advances in the field drug and small molecule delivery such as fluorouracil, folic acid, doxorubicin, paclitaxel, and daunorubicin, specifically when using gold and iron oxide NPs as carriers of anticancer therapeutic agents.
Breast cancer is the most common malignancy worldwide, especially among women, with substantial after-treatment effects. The survival rates of breast cancer have decreased over the years even with the existence of various therapeutic strategies, specifically, chemotherapy. Clinical drugs administered for breast cancer appear to be non-targeting to specific cancer sites leading to severe side effects and potentially harming healthy cells instead of just killing cancer cells. This leads to the need for designing a targeted drug delivery system. Nanomaterials, both organic and inorganic, are potential drug nanocarriers with the ability of targeting, imaging and tracking. Various types of nanomaterials have been actively researched together with their drug conjugate. In this review, we focus on selected nanomaterials, namely solid-lipid, liposomal, polymeric, magnetic nanoparticles, quantum dots, and carbon nanotubes and their drug conjugates, for breast cancer studies. Their advantages, disadvantages and previously conducted studies were highlighted.
Cellulose acetate (CA) is a remarkable biomaterial most extensively used in biomedical applications due to their properties. This review highlighted the synthesis and chemical structure of CA polymer as well as focused on the mechanical, chemical, thermal, biocompatible, and biodegradable properties of electrospun CA nanofibers. These properties are essential in the evaluation of the CA nanofibers and provide information as a reference for the further utilization and improvement of CA nanofibers. Moreover, we have summarized the use of electrospun CA nanofibers in the drug delivery system as a carrier for drugs and classify them according to the drug class, including anti-inflammatory, anticancer, antioxidant, antimicrobial agents, vitamins and amino acids. Our review has been concluded that CA nanofibers cannot wholly be biodegraded within the human body due to the absence of cellulase enzyme but degraded by microorganisms. Hence, the biodegradation of CA nanofibers in vivo has addressed as a critical challenge.
The acrylated palm oil (APO) nanoparticle is a potential product that can be used as carriers in
medical field. The main focus of the present study was to study the potential of the APO
nanoparticles for used in a controlled drug delivery system. The microemulsion system is used as a
medium to incorporate an active substance such as Thymoquinone (TQ) into the APO polymeric
micelle and then the radiation technique is used as a tool for the synthesis of TQ-loaded APO
nanoparticle. The nano-size TQ-loaded APO particles resulted the particle size of less than 150 nm
with spherical in shape. The TQ release profile was carried out in potassium buffer saline (PBS)
solutions (pH 7.4) at 37
oC. And, the zero-order model has been used to determine the mechanism
of the drug release from the corresponding nanoparticles, respectively. The TQ release was found
to be sustained and controlled in pH 7.4. At pH 7.4, the release of TQ followed the zero-order
model. The in-vitro drug release study showed a good prospect of the APO nanoparticle on being a
potential drug carrier as there are toxic against colon cancer cells and not toxic towards normal
cells. This suggested that the APO product produce using this radiation technique can be
developed into different type of carrier systems for controlled drug release applications.
Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of acyclovir-loaded SLNs was four-fold higher than the commercial suspension. Thus, this investigation presented promising results that the method developed for encapsulation of acyclovir offers potential as an alternative pathway to enhance the drug's bioavailability. In conclusion, this study exhibited the feasibility of SLNs as an oral delivery vehicle for acyclovir and therefore represents a new promising therapeutic concept of acyclovir treatment via a nanoparticulate drug delivery system.
Polyethylene glycol functionalized with oxygenated multi-walled carbon nanotubes (O-PEG-MWCNTs) as an efficient nanomaterial for the in vitro adsorption/release of curcumin (CUR) anticancer agent. The synthesized material was morphologically characterized using scanning electron microscopy, Fourier transform infrared spectroscopy and transmission electron microscopy. In addition, the CUR adsorption process was assessed with kinetic and isotherm models fitting well with pseudo-second order and Langmuir isotherms. The results showed that the proposed O-PEG-MWCNTs has a high adsorption capacity for CUR (2.0 × 103 mg/g) based on the Langmuir model. The in vitro release of CUR from O-PEG-MWCNTs was studied in simulating human body fluids with different pHs (ABS pH 5, intestinal fluid pH 6.6 and body fluid pH 7.4). Lastly, to confirm the success compliance of the O-PEG-MWCNT nanocomposite as a drug delivery system, the parameters affecting the CUR release such as temperature and PEG content were investigated. As a result, the proposed nanocomposite could be used as an efficient carrier for CUR delivery with an enhanced prolonged release property. Graphical Abstract ᅟ.